Ruxolitinib-enhanced haploidentical transplant for children and young adults with sickle cell disease

Ruxolitinib-Enhanced Conditioning for Pediatric and Young Adult Patients With Symptomatic Sickle Cell Disease Undergoing Haploidentical Hematopoietic Cell Transplantation

This trial will test whether adding ruxolitinib to a reduced-intensity haploidentical transplant lowers the risk of graft failure in children and young adults with sickle cell disease.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 12 Years to 45 Years
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: ruxolitinib, cyclophosphamide, fludarabine
• Locations: 4 sites (Aurora, Colorado and 3 other locations)
• Trial ID: NCT07252050 on ClinicalTrials.gov

What this trial studies

RUX-HAPLO is a Phase 1/2, single-arm, open-label multi-center trial enrolling up to 24 participants aged 12–45 undergoing haploidentical hematopoietic cell transplant for sickle cell disease. Participants receive cytoreduction with hydroxyurea followed by a reduced-intensity conditioning regimen (cyclophosphamide, fludarabine, thiotepa, ATG and low-dose TBI) and ruxolitinib started during conditioning and continued after transplant. Graft-versus-host disease prophylaxis includes post-transplant cyclophosphamide plus sirolimus or a calcineurin inhibitor. The primary endpoint is 1-year event-free survival with primary or secondary graft failure or death counted as events, and participants are followed for approximately two years post-transplant.

Who should consider this trial

Good fit: Ideal candidates are patients aged 12–45 with any genotype of sickle cell disease who meet high-risk clinical criteria (for example stroke, recurrent acute chest syndrome, recurrent severe pain episodes, or need for chronic transfusions), have an HLA-haploidentical first-degree relative donor, and meet institutional HCT eligibility.

Not a fit: Patients who have an available HLA-matched sibling donor, are outside the 12–45 age range, or have contraindications to hematopoietic cell transplant or ruxolitinib are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce graft failure after haploidentical transplant and increase the chance of a durable cure for pediatric and young adult patients with sickle cell disease.

How similar studies have performed: Haploidentical reduced-intensity transplants have cured many patients with sickle cell disease and JAK inhibition with ruxolitinib has shown benefit for post-transplant inflammatory complications, but using ruxolitinib specifically to reduce graft failure in pediatric SCD is a relatively novel approach with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Participants with any genotypic form of SCD aged 12 - 45 years at enrollment with ≥1 of the following:

   1. History of stroke and/or vasculopathy, including evidence of asymptomatic cerebrovascular disease for pediatric patients.
   2. Recurrent moderate-severe acute chest syndrome (ACS)
   3. Recurrent vaso-occlusive pain episodes requiring parenteral analgesia despite the institution of supportive care.
   4. Need for chronic transfusion therapy to prevent vaso-occlusive complications (i.e. pain, stroke, and ACS).
   5. For adult patients, an echocardiographic finding of tricuspid valve regurgitant jet velocity (TRJV) ≥ 2.7 m/sec.
2. Participants must have an HLA haploidentical first degree relative (parent, sibling, or half sibling) who is willing and able to donate bone marrow.
3. Participants must meet institutional eligibility criteria for HCT.

Exclusion Criteria:

1. Presence of an HLA-matched sibling who is willing and able to donate bone marrow.
2. Uncontrolled infection, evidence of active TB, Hepatitis B or C infection, or HIV seropositivity or infection.
3. Previous HCT or solid organ transplant.
4. CNS revascularization procedure, myocardial infarction, pulmonary embolus or deep vein thrombosis in the past 6 months.
5. Use of medications which significantly interfere with ruxolitinib metabolism.
6. Known hypersensitivity or severe reaction to ruxolitinib or any component of the conditioning regimen or its excipients.
7. Inability to swallow and retain oral medication (use of nasogastric or gastrostomy tube permitted).
8. History of malignancy except resected basal cell carcinoma or treated carcinoma in-situ.
9. Participation in another clinical trial involving an investigational or off-label use of a drug or device in the past 3 months.
10. Currently pregnant or breast feeding.
11. Clinically significant, uncontrolled autoimmune disease.
12. High-titer anti-donor specific HLA antibodies (without review and approval by Study Chair).
13. Participant (or guardian) inability or unwillingness to comply with the dose schedule and study evaluations, comprehend or sign informed consent and utilize a highly effective method of contraception (for participants of child-bearing potential).
14. Any condition that would, in the investigator's judgment, interfere with full participation in the study, pose a significant risk to the subject, or interfere with interpretation of study data.

Where this trial is running

Aurora, Colorado and 3 other locations

• Children's Hospital of Colorado — Aurora, Colorado, United States (Not_yet_recruiting)
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States (Recruiting)
• Manning Family Children's — New Orleans, Louisiana, United States (Not_yet_recruiting)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: Laura McLaughlin, MD — University of Colorado, Denver
• Study coordinator: Laura McLaughlin, MD

Conditions Sickle Cell Disease; Hematopoetic Stem Cell Transplant; Haploidentical Hematopoietic Stem Cell Transplant; Haploidentical Stem Cell Transplantation; Graft Failure; Sickle cell disease; Hematopoietic cell transplant; Ruxolitinib